Key Facts

Bladder cancer has a high recurrence rate for superficial disease and requires lifelong cystoscopic surveillance. Muscle-invasive disease has a significantly worse prognosis.

Epidemiology

• Approximately 10,300 new cases/year in the UK
• Male:female ratio 3:1
• Median age at diagnosis: 73 years
• ~5,500 deaths/year

Aetiology

• Smoking: most important risk factor (50% of cases); 3× increased risk
• Occupational exposure: aromatic amines (rubber, dye, chemical industries) — latency 15-40 years
• Schistosomiasis (S. haematobium): squamous cell carcinoma in endemic areas (Egypt, Middle East)
• Pelvic radiotherapy: previous RT increases risk
• Cyclophosphamide: haemorrhagic cystitis → increased risk
• Chronic catheterisation/irritation: squamous cell carcinoma

Pathophysiology

• NMIBC (75%): confined to mucosa (Ta, CIS) or lamina propria (T1); high recurrence rate (50-70%)
• MIBC (25%): invades muscularis propria (T2) or beyond; higher metastatic potential
• Carcinoma in situ (CIS): flat, high-grade; high progression risk to muscle-invasive disease
• FGFR3 mutations: common in low-grade NMIBC (targeted by erdafitinib)
• P53 mutations: common in high-grade and muscle-invasive disease

Typical Presentation

• Painless visible (macroscopic) haematuria: most common (80-90%)
• Non-visible (microscopic) haematuria
• Lower urinary tract symptoms (frequency, urgency — especially with CIS)
• Recurrent UTIs

Advanced Disease

• Pelvic pain
• Flank pain (ureteric obstruction)
• Lower limb oedema (lymphatic/venous obstruction)
• Bone pain (metastases)
• Weight loss, fatigue

Red Flags

• Visible haematuria in any adult ≥45 (2-week wait referral)
• Non-visible haematuria with raised PSA, UTI symptoms, or recurrent UTIs ≥60
• Palpable suprapubic mass
• Hydronephrosis on imaging

Bedside

• Urinalysis (haematuria)
• DRE (exclude prostate pathology)
• Abdominal examination

Bloods

• FBC, U&Es, LFTs
• PSA (if indicated)

Imaging

• CT urogram: investigation of choice for visible haematuria (detects upper tract tumours)
• USS kidneys and bladder: alternative initial imaging
• CT chest/abdomen/pelvis: staging for MIBC
• MRI pelvis: local staging (T stage assessment)

Special Tests

• Flexible cystoscopy: gold standard for diagnosis; outpatient under local anaesthetic
• TURBT (transurethral resection of bladder tumour): diagnostic (provides tissue) and therapeutic for NMIBC
  • Must include detrusor muscle in specimen to assess muscle invasion
• Urine cytology: useful for high-grade and CIS (low sensitivity for low-grade)
• Re-TURBT: at 6 weeks for high-grade T1 or if detrusor muscle absent from initial specimen

Non-pharmacological

• Smoking cessation (reduces recurrence risk)
• Cystoscopic surveillance post-TURBT
• MDT discussion for all MIBC

Pharmacological

• NMIBC — low/intermediate risk: single dose intravesical mitomycin C 40mg at TURBT
• NMIBC — high risk (T1 high-grade, CIS): intravesical BCG (Bacillus Calmette-Guérin) induction (6 weekly instillations) + maintenance (3 weekly at 3, 6, 12 months)
• MIBC — neoadjuvant chemotherapy: gemcitabine + cisplatin × 3-4 cycles before radical cystectomy (improves 5-year survival by 5-8%)
• Metastatic/advanced: gemcitabine + cisplatin first-line; pembrolizumab or atezolizumab for PD-L1+ cisplatin-ineligible patients; avelumab maintenance after chemo (JAVELIN Bladder 100)
• FGFR-altered: erdafitinib (targeted therapy)
• Enfortumab vedotin (antibody-drug conjugate): for post-ICI/post-chemo advanced urothelial carcinoma

Surgical/Interventional

• TURBT: first-line for NMIBC (diagnostic and therapeutic)
• Radical cystectomy + urinary diversion: standard for MIBC (T2+)
  • Ileal conduit (Bricker) or neobladder reconstruction
  • Includes pelvic lymphadenectomy
• Radical radiotherapy (55Gy/20 fractions): bladder-preserving alternative for MIBC with concurrent chemo (mitomycin C + 5-FU, or gemcitabine)
• Palliative radiotherapy: for haemorrhage, pain
• Nephrostomy: for obstructive uropathy

Referral Criteria

• Visible haematuria ≥45: 2-week wait urology referral
• Non-visible haematuria ≥60 with dysuria or raised WCC: 2-week wait
• All MIBC: MDT discussion

• NMIBC (Ta low-grade): 5-year survival >90%; recurrence rate 50-70% (requires surveillance)
• T1 high-grade: 5-year survival 70-80%; progression to MIBC in 30-50% if inadequately treated
• CIS: high progression risk (50-70% without BCG); BCG response rate 70-80%
• MIBC (T2-T3): 5-year survival 40-60% with radical treatment
• Metastatic: median survival 12-15 months with chemotherapy; improving with immunotherapy
• Overall 5-year survival: approximately 50%
• Lifelong cystoscopic surveillance is required for NMIBC (check cystoscopy at 3 months, then scheduled intervals)

Bladder Cancer Staging (TNM)

Risk Stratification for NMIBC